Genotype and allele frequency of human multidrug resistance (MDR1) gene C3435T polymorphism in Denizli province of Turkey

被引:28
作者
Turgut, Sebahat [1 ]
Turgut, Gunfer
Atalay, Erol Omer
机构
[1] Pamukkale Univ, Dept Physiol, Fac Med, TR-20070 Denizli, Turkey
[2] Pamukkale Univ, Dept Biophys, Fac Med, TR-20070 Denizli, Turkey
关键词
p-glycoprotein; C3435T polymorphism; Turkish population; MDR1;
D O I
10.1007/s11033-006-9022-x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Human p-glycoprotein encoded by human multidrug resistance (MDR1) gene, is a transmembrane protein that serves as efflux pump for a wide variety of lipophilic compounds possessing a physiological role in protecting cells against the DNA damaging of certain xenobiotics. According to the published data, the frequency of C3435T polymorphism differs depending on the different ethnical populations such as Asian, African, and Caucasians populations. In our study, we identified the MDR1 C3435T polymorphism in 150 healthy volunteers in Denizli province of Turkey. DNA was extracted from peripheral blood samples by standard phenol/chloroform extraction method. Polymerase chain reaction-restriction fragment length polymorphism was used for the detection of C3435T single nucleotide polymorphism. We obtained CC, CT and TT genotype frequencies as 20, 53 and 27%, respectively. According to our results, the C allele in Turkish population (Denizli province, west of Turkey) is found 47% and this data shows similarity with Caucasian (UK and German) populations and significantly lower than African populations (p < 0.001). Our study is the first data on the genotype and allele frequency of the human multidrug resistance (MDR1) Gene C3435T Polymorphism in Denizli Province at regional basis in Turkey. Our results could serve as a basis for large-scale correlation studies on the relevance of C3435T genotype in cancer therapy and other diseases in Turkish population. Investigation of genotype frequencies related with p-glycoprotein substrates should be investigated in large scale at regional bases in Turkish population. The scaled-up data might help either to the use of p-glycoprotein substrates to be used for therapeutic applications and population genetics considering the genotype frequencies possibly occurring throughout the history in Anatolian basin.
引用
收藏
页码:295 / 300
页数:6
相关论文
共 35 条
[1]   Biochemical, cellular, and pharmacological aspects of the multidrug transporter [J].
Ambudkar, SV ;
Dey, S ;
Hrycyna, CA ;
Ramachandra, M ;
Pastan, I ;
Gottesman, MM .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 1999, 39 :361-398
[2]   MDR1 pharmacogenetics:: frequency of the C3435T mutation in exon 26 is significantly influenced by ethnicity [J].
Ameyaw, MM ;
Regateiro, F ;
Li, T ;
Liu, XH ;
Tariq, M ;
Mobarek, A ;
Thornton, N ;
Folayan, GO ;
Githang'a, J ;
Indalo, A ;
Ofori-Adjei, D ;
Price-Evans, DA ;
McLeod, HL .
PHARMACOGENETICS, 2001, 11 (03) :217-221
[3]   Frequency distribution of C3435T mutation in exon 26 of the MDR1 gene in a Spanish population [J].
Bernal, ML ;
Sinues, B ;
Fanlo, A ;
Mayayo, E .
THERAPEUTIC DRUG MONITORING, 2003, 25 (01) :107-111
[4]   Targeting an extracellular epitope of the human multidrug resistance protein 1 (MRP1) in malignant cells with a novel recombinant single chain Fv antibody [J].
Binyamin, L ;
Assaraf, YG ;
Haus-Cohen, M ;
Stark, M ;
Reiter, Y .
INTERNATIONAL JOURNAL OF CANCER, 2004, 110 (06) :882-890
[5]   Pharmacogenetics of the human drug-transporter gene MDR1:: impact of polymorphisms on pharmacotherapy [J].
Brinkmann, U ;
Roots, I ;
Eichelbaum, M .
DRUG DISCOVERY TODAY, 2001, 6 (16) :835-839
[6]   Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDR1 gene in white subjects [J].
Cascorbi, I ;
Gerloff, T ;
Johne, A ;
Meisel, C ;
Hoffmeyer, S ;
Schwab, M ;
Schaeffeler, E ;
Eichelbaum, M ;
Brinkmann, U ;
Roots, I .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 2001, 69 (03) :169-174
[7]  
CHEN CJ, 1990, J BIOL CHEM, V265, P506
[8]   P-glycoprotein and multidrug resistance [J].
Gottesman, MM ;
Pastan, I ;
Ambudkar, SV .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 1996, 6 (05) :610-617
[9]   Disruption of P-glycoprotein anticancer drug efflux activity by a small recombinant single-chain Fv antibody fragment targeted to an extracellular epitope [J].
Haus-Cohen, M ;
Assaraf, YG ;
Binyamin, L ;
Benhar, I ;
Reiter, Y .
INTERNATIONAL JOURNAL OF CANCER, 2004, 109 (05) :750-758
[10]   Functional polymorphisms of the human multidrug-resistance gene:: Multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo [J].
Hoffmeyer, S ;
Burk, O ;
von Richter, O ;
Arnold, HP ;
Brockmöller, J ;
Johne, A ;
Cascorbi, I ;
Gerloff, T ;
Roots, I ;
Eichelbaum, M ;
Brinkmann, U .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (07) :3473-3478